Molecular Networking-Based Screening Led to the Discovery of a Cyclic Heptadepsipeptide from an Endolichenic Xylaria sp.

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic Xylaria sp. The main component, xylaroamide A ( 1 ), was obtained by LC-MS-guided isolation. The planar structure of compound 1 was elucidated via 1D and 2D NMR, as well as MS/MS data. The configurations were fully determined by the combination of advanced Marfey's analysis, partial hydrolysis, Mosher's reaction, and GIAO NMR calculation based on a restricted conformational search. A plausible biosynthetic pathway for xylaroamide A ( 1 ) involving a rare trans -acting N -methyltransferase is proposed based on bioinformatics analysis. Xylaroamide A ( 1 ) exhibited inhibitory activity against cancer cell lines BT-549 and RKO with IC ₅₀ values of 2.5 and 9.5 μM, respectively.